Inverse Peptide Synthesis via Activated [alpha]-Aminoesters

A mild, practical, and simple procedure for peptide-bond formation is reported. Instead of activation of the carboxylic acid functionality, the reaction involves an unprecedented use of activated [alpha]-aminoesters. The method provides a straightforward entry to dipeptides and was effective when a sensitive cysteine residue was used, as no epimerization was detected in this case. The applicability of this method to iterative peptide synthesis was illustrated by the synthesis of a model tetrapeptide in the challenging reverse N[arrow right]C direction. [PUBLICATION ABSTRACT]